Bone marrow mesenchymal stem cells from leukemia patients inhibit growth and apoptosis in serum-deprived K562 cells
The regulation of growth and apoptosis in K562 cells by human bone marrow mesenchymal stem cells (MSCs) from leukemia patients was investigated.
Methods: K562 cells were cocultured with leukemic MSCs under serum deprivation.
Cell Counting Kit-8 (CCK-8), PI staining, Annexin V/PI binding and FACS assays were used to investigate cell proliferation, cell cycle status, and apoptosis of K562 cells cultures in the presence or absence of 10% serum. Western blotting was used to determine the levels of Akt, phosphorylated Akt (p-Akt), the BCL-2 family member Bad, and phosphorylated Bad (p-Bad) proteins in K562 cells after coculturing with MSCs.
The effects of LY294002 (a specific inhibitor of PI3K) on protein expression were also determined.
Results: K562 cell proliferation was inhibited by coculture with MSCs and the dominant cell cycle was the G0-G1 phase.
The proportion of apoptotic K562 cells was decreased and the levels of p-Akt and p-Bad were upregulated after exposing K562 cells to MSCs. However, when LY294002 was used, p-Akt and p-Bad proteins inK562 cells showed a significant reduction, while no distinct variation was seen in the nonphosphorylated Akt and Bad protein levels.
Conclusions: Leukemic MSCs can inhibit K562 cell expansion and modulate the cell cycle to a state of relative quiescence. This allows the K562 cells to endure adverse conditions such as serum starvation.
The PI3K-Akt-Bad signaling pathway may be involved in this antiapoptotic process via phosphorylation of the Akt and Bad proteins. Blocking MSC-induced transduction of the PI3K-Akt-Bad pathway may be a potential strategy for a targeted therapy to combat leukemia.
Author: Zhaohui WeiNaiyao ChenHongxing GuoXueming WangFangyun XuQian RenShiHong LuBin LiuLei ZhangHui Zhao
Credits/Source: Journal of Experimental &Clinical Cancer Research 2009, 28:141
Published on: 2009-11-03
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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